title: ERK1/2 regulates SIRT2 deacetylase activity.
abstract: SIRT2 is a mammalian member of the Sirtuin family of NAD-dependent protein deacetylases. The function of SIRT2 can be modulated by post-translational modification. However, the precise molecular signaling mechanisms of SIRT2 and extracellular signal-regulated kinase (ERK)1/2 have not been correlated. We investigated the potential regulation of SIRT2 function by ERK1/2. ERK activation by the over-expression of constitutively active MEK increased protein levels and enhanced the stability of SIRT2. In contrast, U0126, an inhibitor of mitogen-activated kinase kinase, suppressed SIRT2 protein level. ERK1/2 interacted with SIRT2 exogenously and endogenously. Deacetylase activity of SIRT2 was up-regulated in an ERK1/2-mediated manner. These results suggest that ERK1/2 regulates SIRT2 by increasing the protein levels, stability and activity of SIRT2.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Yun-Hye
authors.initials: YH
authors.lastname: Jin
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D004789:Enzyme Activation; D004795:Enzyme Stability; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D056565:Sirtuin 2 / Q000378:metabolism*
chemical_list: C474199:SIRT2 protein, human; D056565:Sirtuin 2
keywords: Deacetylation; ERK1/2; Protein level; SIRT2; Stability